Key result
The crystal structure of yeast CDD1 at 2.0-Å resolution and comparative modeling of APOBEC-1 and AID reveal that dimerization and trans-acting loops are required for active site formation and substrate selectivity.
Dimerization requirements for APOBEC-1 clarified; extends molecular models but leaves open any therapeutic targeting in lipid disorders.
Activation-induced deaminase (AID) uses base deamination for class-switch recombination and somatic hypermutation and is related to the mammalian RNA-editing enzyme apolipoprotein B editing catalytic subunit 1 (APOBEC-1). CDD1 is a yeast ortholog of APOBEC-1 that exhibits cytidine deaminase and RNA-editing activity. Here, we present the crystal structure of CDD1 at 2.0-A resolution and its use in comparative modeling of APOBEC-1 and AID. The models explain dimerization and the need for trans-acting loops that contribute to active site formation. Substrate selectivity appears to be regulated by a central active site "flap" whose size and flexibility accommodate large substrates in contrast to deaminases of pyrimidine metabolism that bind only small nucleosides or free bases. Most importantly, the results suggested both AID and APOBEC-1 are equally likely to bind single-stranded DNA or RNA, which has implications for the identification of natural AID targets.
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Xie et al. (2004) studied this question. ScCDD1 crystal structure and comparative modeling was evaluated on Crystal structure of CDD1 and comparative modeling of APOBEC-1 and AID. The crystal structure of yeast CDD1 at 2.0-Å resolution and comparative modeling of APOBEC-1 and AID reveal that dimerization and trans-acting loops are required for active site formation and substrate selectivity.
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